Self-Amplifying Pestivirus Replicon RNA Encoding Influenza Virus Nucleoprotein and Hemagglutinin Promote Humoral and Cellular Immune Responses in Pigs.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Thomann-Harwood, Lisa J
Guzmán, Carlos A
McCullough, Kenneth C
MetadataShow full item record
AbstractSelf-amplifying replicon RNA (RepRNA) promotes expansion of mRNA templates encoding genes of interest through their replicative nature, thus providing increased antigen payloads. RepRNA derived from the non-cytopathogenic classical swine fever virus (CSFV) targets monocytes and dendritic cells (DCs), potentially promoting prolonged antigen expression in the DCs, contrasting with cytopathogenic RepRNA. We engineered pestivirus RepRNA constructs encoding influenza virus H5N1 (A/chicken/Yamaguchi/7/2004) nucleoprotein (Rep-NP) or hemagglutinin (Rep-HA). The inherent RNase-sensitivity of RepRNA had to be circumvented to ensure efficient delivery to DCs for intracellular release and RepRNA translation; we have reported how only particular synthetic delivery vehicle formulations are appropriate. The question remained concerning RepRNA packaged in virus replicon particles (VRPs); we have now compared an efficient polyethylenimine (PEI)-based formulation (polyplex) with VRP-delivery as well as naked RepRNA co-administered with the potent bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) adjuvant. All formulations contained a Rep-HA/Rep-NP mix, to assess the breadth of both humoral and cell-mediated defences against the influenza virus antigens. Assessment employed pigs for their close immunological relationship to humans, and as natural hosts for influenza virus. Animals receiving the VRPs, as well as PEI-delivered RepRNA, displayed strong humoral and cellular responses against both HA and NP, but with VRPs proving to be more efficacious. In contrast, naked RepRNA plus c-di-AMP could induce only low-level immune responses, in one out of five pigs. In conclusion, RepRNA encoding different influenza virus antigens are efficacious for inducing both humoral and cellular immune defences in pigs. Comparisons showed that packaging within VRP remains the most efficacious for delivery leading to induction of immune defences; however, this technology necessitates employment of expensive complementing cell cultures, and VRPs do not target human cells. Therefore, choosing the appropriate synthetic delivery vehicle still offers potential for rapid vaccine design, particularly in the context of the current coronavirus pandemic.
CitationFront Immunol. 2021 Jan 28;11:622385. doi: 10.3389/fimmu.2020.622385.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
JournalFrontiers in immunology
The following license files are associated with this item:
- Creative Commons
- Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines.
- Authors: Démoulins T, Milona P, Englezou PC, Ebensen T, Schulze K, Suter R, Pichon C, Midoux P, Guzmán CA, Ruggli N, McCullough KC
- Issue date: 2016 Apr
- Self-replicating RNA vaccine functionality modulated by fine-tuning of polyplex delivery vehicle structure.
- Authors: Démoulins T, Ebensen T, Schulze K, Englezou PC, Pelliccia M, Guzmán CA, Ruggli N, McCullough KC
- Issue date: 2017 Nov 28
- Self-Amplifying Replicon RNA Delivery to Dendritic Cells by Cationic Lipids.
- Authors: Englezou PC, Sapet C, Démoulins T, Milona P, Ebensen T, Schulze K, Guzman CA, Poulhes F, Zelphati O, Ruggli N, McCullough KC
- Issue date: 2018 Sep 7
- Self-replicating Replicon-RNA Delivery to Dendritic Cells by Chitosan-nanoparticles for Translation In Vitro and In Vivo.
- Authors: McCullough KC, Bassi I, Milona P, Suter R, Thomann-Harwood L, Englezou P, Démoulins T, Ruggli N
- Issue date: 2014 Jul 8
- Self-Replicating RNA Vaccine Delivery to Dendritic Cells.
- Authors: Démoulins T, Englezou PC, Milona P, Ruggli N, Tirelli N, Pichon C, Sapet C, Ebensen T, Guzmán CA, McCullough KC
- Issue date: 2017